SECTION N3/PR0JECT 1/ALIVISATOS PI: Gambhir, Sanjiv S N3.1.1. Project Summary: The long-term goal of PI is to engineer, synthesize, characterize and optimize the next generation nanoparticle platforms that can potentially be translated clinically to develop nanodiagnostics and imaging agents for in vitro and in vivo use for the improved management of cancer. The role of PI in the overall scheme of this CCNE-T application is shown in Fig. N3.1.1, Our primary focus for this CCNE application is to develop and use nanotechnology for monitoring response to anti-cancer therapy and for earlier cancer detectior\. Our cancer focus in the current proposal is on both lung and ovarian cancers but expect that our strategies will eventually apply to many cancers. Both in vitro nanosensors and in vivo nanomolecular imaging will be utilized to accomplish our long-term goals. The combination of both In vitro and In vivo diagnostic strategies is expected to lead to a much greater accuracy and cost-effectiveness than either strategy alone. To translate our in vitro and in vivo diagnostic strategies we will utilize mouse models that help us to test our approaches prior to clinical translation. The clinical translation will be accomplished through the clinical translation core (Core 3) which links to various clinical trials and leverages on other funding mechanisms already in place in our CCNE. In order to meet the improved nanoparticle needs of our other proposed Research Projects, PI will be focusing on the development of these newer types of nanoparticles and nano-strategies as described in sections below. We envision that these new types of nanoparticles will have outstanding advantages for biomedical imaging and the development of in vitro diagnostics such as for multimodal imaging, multiplexing, multi-effector functionalities, improved signal amplification via outstanding signal to noise ratio characteristics of the to-be-developed nanocrystals. These advantages are especially valuable with clinical biological fluid samples which always present significant challenges. Thus, the focus of P1 will be the realization of the next generation nanoparticles, their in vitro , characterization in cell culture models, and the delivery of these nanoparticles to the other projects for further detailed studies to assess cancer iviodeis& their utility as cancer diagnostics and cancer imaging agents. This project also fulfills the requirement of the CCNE RFA wherein a basic research project with nanotechnology discovery was listed as one of the required projects. Being a fundamental nanoscience Figure N3.1.1. The thematic discovery project, the proposed P1 meets this condition. The PI consists areas ofthe projects and of two Discovery Nanotechnology sub-projects, as described below